Beraprost sodium is a prostacyclin (PGI2) derivative having a vasodilating action and a platelet aggregation inhibition action, which is used for improving ulcer, pain, and coldness associated with arteriosclerosis obliterans or thromboangiitis obliterans and widely distributed in the market as an oral formulation. However, an oral administration of the drug rapidly elevates its blood level and causes side effects such as facial flushing, hot flash, headache dull, and anorexia.
Recently, a patch draws attention as a formulation for administering the drug in a body in the light of ease in handling or dosage management. Such a transdermal absorption-type formulation is expected to suppress the rapid elevation of the blood level, maintain the stable blood level, and thus reduce the side effects.
Generally, transdermal absorption-type formulations can be classified into the following types.
(1) an oily patch, which is prepared by adding an active ingredient to an adhesive base (an oily base) comprising a water-insoluble natural or synthetic polymer compound such as a resin, a plastic, and a rubber as the main base, a softener, a tackifier resin, and optionally other ingredients, followed by homogeneously stirring the obtained mixture, and then spreading it on or enclosing it in a fabric or a plastic film to form a patch;(2) an aqueous patch, which is prepared by mixing and kneading a natural or synthetic polymer compound such as a water-soluble polymer and a water-absorbing polymer, other ingredients such as glycerin, and purified water (hereinafter also referred to as “water”), followed by adding an active ingredient to the obtained mixture and homogeneously stirring it, and then spreading it on a backing or a liner such as a fabric to form a patch; and(3) a non-aqueous patch, which is prepared by mixing and kneading ingredients such as polyacrylic acid and a polyhydric alcohol, followed by adding an active ingredient to the obtained mixture and homogeneously stirring it, and then spreading it on a backing or a liner such as a fabric to form a substantially water-free patch.
Beraprost or a pharmacologically acceptable salt thereof has been mainly and variously developed as an oily patch until now. For example, Patent Document 1 discloses an oily patch comprising beraprost and saturated fatty acid or unsaturated fatty acid and Patent Document 2 discloses an oily patch comprising this drug and a fatty alcohol having 14 to 20 carbon atoms as an absorption enhancer. However, the affinity of beraprost for an oily base in an oily patch becomes too high, and desired transdermal absorption cannot be achieved. Further, if an absorption enhancer is added to an oily patch to improve the transdermal absorption of the drug, the formulation properties become worse.